Innate immune response after acute myocardial infarction and pharmacomodulatory action of tacrolimus in reducing infarct size and preserving myocardial integrity

Abstract

BackgroundThis study investigated the association between innate immune reaction and myocardial damage after acute myocardial infarction (AMI) and anti-inflammatory role of tacrolimus in reducing infarct size. Male mini-pigs (n=18) were equally categorized into sham control (SC), untreated AMI (by ligation of left anterior descending coronary artery), and AMI-Tacrolimus (AMI-Tac) (0.5 mg intra-coronary injection 30 minutes post-AMI). Cardiac magnetic resonance imaging (MRI) was performed at post-AMI days 2, 5 and 21 before sacrificing the animals.ResultsBy post-AMI day 21, left ventricular ejection fraction (LVEF) was lowest in untreated AMI animals, significantly higher in SC than in AMI-Tac group (all p<0.003). Infarct areas at basal, middle, and apical levels, numbers of CD14+ and iNOS+ cells in infarct area (IA) and peri-IA, and protein expression of CD14, CD68, and Ly6g from circulating inflammatory cells showed an opposite pattern compared with that of LVEF in all groups (all p<0.005). Protein expressions of MCP-1, MIP-1, TNF-α, NF-κB, iNOS, and IL-12 in IA and peri-IA exhibited an identical pattern compared to that of CD14, CD68, and Ly6g from circulating inflammatory cells (all p<0.01). Expressions of myocardial damage biomarkers in IA and peri-IA [γ-H2AX, β-myosin heavy chain (MHC), Smad3, TGF-β] were highest in AMI and higher in AMI-Tac than in SC, whereas expressions of myocardial integrity biomarkers (connexin43, mitochondrial cytochrome-C, α-MHC, BMP-2, Smad1/5) were opposite to those of damage biomarkers (all p<0.001).ConclusionInnate immune responses were markedly augmented and LVEF was significantly reduced after AMI but were remarkably improved after tacrolimus treatment.

Therapeutic Potential of Tacrolimus on Acute Myocardial Infarction in Minipigs: Analysis with Serial Cardiac Magnetic Resonance and Changes at Histological and Protein Levels

“…The present study supports that intracoronary tacrolimus therapy harboring therapeutic potential against AMI in minipigs by monitoring in vivo temporal changes of infarct on serial CMR examinations [9–11]. Our results revealed significant progressive impairment of LVF and contractility on CMR from day 2 to day 21 among controls.…”

Cardiac stem cell transplantation with 2,3,5,4′-tetrahydroxystilbehe-2-O-β-d-glucoside improves cardiac function in rat myocardial infarction model

“…Living tissue stained a deep-red color with TTC, whereas infarcted tissue remained white. This allowed confirmation of the MI size, and quantified with the ratio of the total area of the infarct size to the total area of the whole heart for five sections [33,34].…”

Experimental Methodology of Inflammatory Factors Induced by Anaesthetics in Myocardial Ischemia

“…Since AMI elicits prompt tissue necrosis and inflammation, it is conceivable that innate immunity has an important role to play a rapidly immune-inflammatory response, especially at the early phase of AMI. Surprisingly, while the link between AMI and inflammatory reaction has been investigated in depth [1][2][3][4][5][6][7], the involvement of the innate immune system in inflammation after AMI has only been seldom reported [5,7,8]. Efficient inflammation is required for host defense against damage and tissue repair.…”